This invention relates to a novel process for producing 7-alkoxycarbonyl-6,8-dimethyl-4-hydroxymethyl-1-phthalazone, as well as to its intermediates.
7-Alkoxycarbonyl-6,8-dimethyl-4-hydroxymethyl-1-phthalazone (hereinafter referred to as 4-hydroxymethyl-1-phthalazone) represented by the following formula: ##STR1## wherein R.sub.1 is a lower alkyl, is a compound originally produced by Shimamoto, Ishikawa et al. through a structure-activity relationship study of a series of compounds having phthalazone skeleton. Having a very strong inhibitory action on the coagulation of blood platelets and an inhibitory action on phosphodiesterase, this compound is expected as an effective therapeutic medicine for cerebral hemorrhage, atherosclerosis and cerebral apolexy (U.S. Pat. No. 3,963,716; Austrian Pat. No. 7,408,744).
The process mentioned in the above-mentioned patent has a fault that mass production of the objective compound is difficult because the starting compound itself is difficult to synthesize.
For example, in the process for synthesizing 5,7-dimethyl-6-ethoxycarbonyl-3-hydroxy-3-methylphthalide (B) by reacting 3,5-dimethyl-4-ethoxycarbonylphthalic anhydride (A) with dimethylcadmium as shown in the following scheme: ##STR2## the cadmium is a dangerous heavy metal and the reaction requires to use a large quantity of ether under an anhydrous condition, so that the process is undesirable as an industrial production process.
In the process for synthesizing the phthalide derivative (B) by reacting the above-mentioned phthalic anhydride derivative (A) with malonic acid (Japanese Patent Kokai (Laid-Open)) No. 84,563/1975) a position isomer (C) represented by the following formula: ##STR3## is formed as a by-product.
The present inventors found out a process suitable for mass production and having no faults mentioned above.
According to the process of this invention, the objective compound can be obtained from an inexpensive starting material in a high yield.